Can we make injectable materials that are as tough as the tissues that they are intended to replace?

Hi all,

I’d like to utilise this platform to pose the question as titled, and hopefully stimulate some discussion around alternative methods for the following point…

My specific area of interest is around mechanical properties of injectable materials, as well as host response. These are ‘old questions’ if you like, but remain unanswered. Many of the injectable materials have mechanical properties far inferior to the biological tissues that they replace. The answer to this question, in my opinion, comes down to molecular weight and molecular interactions but many of the processes that turn low molecular weight polymers into high molecular weight (or crosslinked) polymers require highly toxic species (initiators, crosslinkers, etc) but is there a more biologically friendly way of doing this?

I very much look forward to hearing your thoughts.

Kind regards,
Owen.

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Hi Owen,
What’s about using complexation with metal? eg calcium induced alginate gelation. It’s a kind of reversible crosslink but I guess more friendly than acrylate. Cellink company uses this technique to strengthen the 3D object after printing

Regards,

Thomas

Hi Thomas,

Thanks for your reply. Glad that you choose that material to discuss as it is one I have considerable interest in. Sure, metal ions can certainly increase interactions between alginate chains, producing a degree of stiffness to the hydrogels. We can also use other ions like gallium, aluminium, barium; which seem to produce materials with better strengths. However, these physical/ionic crosslinks have limited strengths and toughness remains relatively low compared to covalently crosslinked hydrogels like pHEMA.

Particularly when we look at orthopaedic cements like PMMAs; even at these relatively high molecular weights the materials remain quite brittle compared to the biological materials that they replace.

Are there ways of producing these high molecular weight materials that do not include the problematic side-effects of cytotoxicity? Can we utilise ‘click chemistry’ or some other chemistry to produce strong, stable covalent bonds, without the side-effects?

Regards,

Owen

Hi Owen,

It is pretty straightforward to crosslink covalently whatever functional groups you want, using biocompatible crosslinkers. There are many simple strategies no need to use click chemistry if you do not want.

PMMA is different though.

Regards
Maurice.

Hi Maurice,

Thanks for your input. Can you discuss some of these strategies in more detail?

Regards,

Owen

Hi Oven,

It’s also my interest to enhance the mechanical properties of injectable chitosan-based hydrogels without using chemical crosslinkers. The physically crosslinked hydrogels made by natural polymers relatively weaker.
However, some strategies might provide enhancement of gelation and mechanical properties;

  1. making polycomplexes by adding oppositely charged another natural polymer can be an alternative but it should be in a controlled way to achieve final homogeneous solution properties and preventing precipitation
  2. in our chitosan-based hybrid hydrogels integrated with hydroxyapatite minerals, we could achieve enhancement at mechanical strength by adding a polyol-plasticizer, as well as increasing the pH to above a certain level by using a weak base in a pH and temperature-sensitive gelation system.
    Using a hydroalcoholic media induced the hydrophobic interactions in solution, and this led to increase at gelation speed, compression strength and gel flexibility.

I hope this could be helpful

Best regards

Fatma

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Fatma,

Thanks for your reply and sharing your interesting approaches. Injectability is a difficult property to achieve with most materials but my feeling is that to achieve high toughness in our injectable materials we need the resultant set material to have a high molecular weight with some interchain movement to allow plasticity at the crack tip, combined with relatively strong bonding within the polymer chains. The issue is (as I see it) that though we could produce these long chained polymers there is little hope of injectability unless polymerisation can occur in a biologically friendly way in vivo. Could a ‘click chemistry’ or other approach make this in situ high molecular weight material possible? Interested to hear anyone’s opinion or suggestions.

Regards,

Owen

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Hi Oven,
Injectable biomaterials are interesting in various biomedical fields. One of my interested research topic is fabrication of functional injectable biomaterials for delivering cells and drugs. In my previous study, we can construct the biomaterials with an interconnected porous structure before injection, which endows the fabricated biomaterials with shape-memory property and tunable mechanical property. The shape-memory biomaterials can be injected to the target sites by using the injection syringe.
I hope this could be helpful
Best regards
Jie Tao

Hi Jie,

That’s very interesting. You might post a link to the study. I assume that these porous sponges are not designed for load-bearing applications? That does raise another interesting topic though; porosity. Which is quite important for a number of applications, such as bone ingrowth or angiogenesis. However, as the pores act as stress raisers in the material this puts a further onus on the materials to be exceptionally tough, which is particularly challenging for injectable materials. Even materials like PMMA cements, when made porous exhibit quite poor toughness.

Double-network hydrogels offer an interesting possibility for tough biocompatible materials but I have not seen any evidence of injectable versions of these and some of the typical crosslinking products could be problematic for in situ setting applications.

Regards,

Owen